Phase I Study of the Safety, Tolerance, and Pharmacokinetics of FK463 in Immunocompromised Children With Fever and Neutropenia

March 3, 2008 updated by: National Cancer Institute (NCI)
The objective of this study is to evaluate the safety, tolerance, and pharmacokinetics of FK463, a novel echinocandin (cell wall-active antifungal lipopeptide), as early empirical therapy for prevention of fungal infections in immunocompromised children. The study is designed as a multicenter open label, sequential dose escalation study of intravenous FK463. Intravenous FK463 will be administered daily as an hour infusion to patients with new onset of fever and neutropenia (absolute neutrophil count less than or equal to 500/mm3) who will be initiated onto broad spectrum empirical antibacterial therapy. The patient population consists of children ages 2 to 17 years of age; two age cohorts will be studied (2-12, 13-17). Dosage levels will be 0.5mg/kg/day (not to exceed 25 mg/day), 1.0 mg/kg/day (not to exceed 50 mg/day), 1.5 mg/kg/day (not to exceed 75 mg/day) and 2.0mg/kg/day (not to exceed 100mg/day). The planned sample size is 64 patients (a maximum of two replacement patients may be added to a given dose level and age cohort, for a total of no more than 10 patients per dose level and age cohort. The study will enroll no more than 80 patients). At each dosage level, a total of 8 patients will be enrolled into each age cohort (2-12, 13-17); a total of 16 patients will be enrolled into each dosage level. The first group of patients will receive FK463 at 0.5 mg/kg/day (not to exceed 25 mg/day). The second group of patients will receive 1.0 mg/kg/day (not to exceed 50mg/day). The third group of patients will receive 1.5 mg/kg/day (not to exceed 75 mg/day). The fourth group of patients will receive 2.0mg/kg/day (not to exceed 100mg/day). Study drug will continue until recovery from neutropenia (ANC post nadir greater than or equal 250/mm3) or until the initiation of conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B for empirical antifungal therapy or for proven fungal infection. Patients may receive FK463 for a maximum duration of 14 days. For any patient who meets institutional criteria to start standard empirical antifungal therapy with conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B (greater than 96 hours on study drug) or who has a proven breakthrough fungal infection, FK463 will be discontinued and conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B will be initiated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The objective of this study is to evaluate the safety, tolerance, and pharmacokinetics of FK463, a novel echinocandin (cell wall-active antifungal lipopeptide), as early empirical therapy for prevention of fungal infections in immunocompromised children. The study is designed as a multicenter open label, sequential dose escalation study of intravenous FK463. Intravenous FK463 will be administered daily as a one hour infusion to patients with new onset of fever and neutropenia (absolute neutrophil count less than or equal to 500/mm3) who will be initiated onto broad spectrum empirical antibacterial therapy. The patient population consists of children ages 2 to 17 years of age; two age cohorts will be studied (2-12, 13-17). Dosage levels will be 0.5 mg/kg/day (not to exceed 25 mg/day), 1.0 mg/kg/day (not to exceed 50 mg/day), 1.5 mg/kg/day (not to exceed 75 mg/day). 2.0 mg/kg/day (not to exceed 100 mg/day), 3.0 mg/kg/day (not to exceed 150 mg/day) and 4.0 mg/kg/day (not to exceed 200 mg/day). The planned sample size is 96 patients (a maximum of two replacement patients may be added to a given dose level and age cohort, for a total of no more than 10 patients per dose level and age cohort. The study will enroll no more than 120 patients). At each dosage level, a total of 8 patients will be enrolled into each age cohort (2-12, 13-17); a total of 16 patients will be enrolled at each dosage level. The first group of patients will receive FK463 at 0.5 mg/kg/day (not to exceed 25 mg/day). The second group of patients will receive 1.0 mg/kg/day (not to exceed 50 mg/day). The third group of patients will receive 1.5 mg/kg/day (not to exceed 75 mg/day). The fourth group of patients will receive 2.0 mg/kg/day (not to exceed 100 mg/day). The fifth group of patients will receive 3.0 mg/kg/day (not to exceed 150 mg/day). The sixth group of patients will receive 4.0 mg/kg/day (not to exceed 200 mg/day). Study drug will continue until recovery from neutropenia (ANC post nadir greater than or equal 250/mm3) or until the initiation of conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B for empirical antifungal therapy or for proven fungal infection. Patients may receive FK463 for a maximum duration of 14 days. For any patient who meets institutional criteria to start standard empirical antifungal therapy with conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B (greater than 96 hours on study drug) or who has a proven breakthrough fungal infection, FK463 will be discontinued and conventional deoxycholate amphotericin B or a lipid formulation of amphotericin B will be initiated.

Study Type

Interventional

Enrollment

120

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Cancer Institute (NCI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Children ages 2-17 with neutropenia (absolute count less than or equal 5000/mm(3)) and one or more of the following conditions: leukemia or lymphoma, excluding those patient's on maintenance therapy; bone marrow or peripheral stem cell transplantation; aplastic anemia; myelodysplastic syndrome; chemotherapy anticipated to incur greater than 10 days of neutropenia.

Patients with new onset of fever during neutropenia who will be initiated onto broad spectrum empirical antibacterial therapy.

Patients must have sufficient venous access to permit administration of study drug, collection of pharmacokinetic samples and monitoring of safety variables.

Concomitant therapies: Patients may have received or continue to receive antineoplastic therapies and medications for supportive care.

Females of childbearing potential must have a negative pregnancy test and must agree to use barrier methods of contraception throughout the study.

Informed consent of the patient, parent, or legally authorized representative obtained prior to entry.

Verbal assent will be obtained from minors capable of understanding.

No patients with active proven deeply invasive fungal infection.

No patients with moderate or severe liver disease, as defined by: AST or ALT greater than 2.5 times the upper limit of normal or total bilirubin greater than 2.5 times the upper limit of normal.

No patients who have received intravenous amphotericin B or formulations of amphotericin B within 72 hours of entering the study or who require treatment with systemic antifungal agents other than FK463. Patients may continue to receive fluconazole prophylactically (no more than 400mg/day or 12mg/kg/day) while on study. All other systemic antifungals agents must be discontinued prior to the first dose of FK463.

No patients who are on other phase I trials of investigational agents.

No patients previously enrolled into this study.

No other concomitant condition which, in the opinion of the investigator, would preclude a patient's participation in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1998

Study Completion

September 1, 2000

Study Registration Dates

First Submitted

November 3, 1999

First Submitted That Met QC Criteria

December 9, 2002

First Posted (ESTIMATE)

December 10, 2002

Study Record Updates

Last Update Posted (ESTIMATE)

March 4, 2008

Last Update Submitted That Met QC Criteria

March 3, 2008

Last Verified

October 1, 1999

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 990007
  • 99-C-0007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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